Katzourou, Ioanna, Barroso, Ines, Benger, Lauren, Ingason, Andres, Stow, Daniel, Tsang, Ruby, Wood, Megan, Kirov, George  ORCID: https://orcid.org/0000-0002-3427-3950, Walters, James ORCID: https://orcid.org/0000-0002-6980-4053, Owen, Michael J. ORCID: https://orcid.org/0000-0003-4798-0862, Holmans, Peter ORCID: https://orcid.org/0000-0003-0870-9412, Van den Bree, Marianne B.M ORCID: https://orcid.org/0000-0002-4426-3254 and Consortium, LINC
2025.
Contributions of common and rare genetic variation to different measures of mood and anxiety disorder in UK Biobank.
BJPsych Open
11
(3)
, e97.
10.1192/bjo.2025.43
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Abstract
Mood and anxiety disorders co-occur and share symptoms, treatments and genetic risk, but it is unclear whether combining them into a single phenotype would better capture genetic variation. The contribution of common genetic variation to these disorders has been investigated using a range of measures, however the differences in their ability to capture variation remain unclear, while the impact of rare variation is mostly unexplored. Aims: We aimed to explore the contributions of common genetic variation and Copy Number Variations associated with risk of psychiatric morbidity (P-CNVs) to different measures of internalising disorders. Method: We investigated eight definitions of mood and anxiety disorder, and a combined internalising disorder, derived from self-report questionnaires, diagnostic assessments, and electronic healthcare data (EHR). Association of these definitions with polygenic risk scores (PRSs) of major depressive disorder and anxiety disorder, as well as presence of a P-CNV, was assessed. Results: The effect sizes of both PRSs and P-CNVs were similar for mood and anxiety disorder. Compared to mood and anxiety disorder, internalising disorder resulted in higher prediction accuracy for PRSs, and increased significance of associations with P-CNVs for most definitions. Comparison across the eight definitions showed that PRSs had higher prediction accuracy and effect sizes for stricter definitions, whereas P-CNVs were more strongly associated with EHR- and self-report- based definitions. Conclusions: Future studies may benefit from using a combined internalising disorder phenotype, and may need to consider that different phenotype definitions may be more informative depending on whether common or rare variation is studied.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Professional Services > Advanced Research Computing @ Cardiff (ARCCA) Schools > Medicine |
| Publisher: | Cambridge University Press |
| ISSN: | 2056-4724 |
| Date of First Compliant Deposit: | 30 April 2025 |
| Date of Acceptance: | 24 February 2025 |
| Last Modified: | 20 Jun 2025 15:29 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/177881 |
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